outline the main stages in the process of cell signalling leading to specific responses: secretion of specific chemicals (ligands) from cells, transport of ligands to target cells, binding of ligands to cell surface receptors on target cells

Fluid‑Mosaic Model of the Plasma Membrane

• Basic structure: A phospholipid bilayer with hydrophilic head‑groups facing the extracellular fluid (ECF) and the cytoplasm, and a hydrophobic core of fatty‑acid tails.
• Key intermolecular forces:

  • Hydrophilic heads – hydrogen‑bonding and ion‑dipole interactions with water.
  • Hydrophobic tails – van der Waals forces that create the non‑polar interior.

• Major membrane components and their functional roles (Cambridge 4.1):

  • Cholesterol – fits between phospholipid tails; buffers membrane fluidity by preventing solidification at low temperature and excessive fluidity at high temperature (temperature‑dependent fluidity).
  • Glycolipids & glycoproteins – carbohydrate chains extend into the ECF; provide cell‑recognition, antigenic specificity and protection (cell‑surface antigens).
  • Integral (transmembrane) proteins – span the bilayer; include receptors, channels and transporters that mediate signalling and selective permeability.
  • Peripheral proteins – attached to the inner or outer surface; often act as enzymes, scaffolds for the cytoskeleton or participants in signalling cascades.

Cell Signalling – Three Main Stages (Cambridge 4.1.3)

1. Synthesis and Secretion of Specific Chemicals (Ligands)

• Typical ligands: hormones, neurotransmitters, cytokines, growth factors.
• Site of synthesis:

  • Peptide / protein ligands – ribosomes → rough ER → Golgi apparatus.
  • Steroid hormones – synthesized in the cytoplasm or smooth ER; no vesicular packaging required.

• Packaging (peptide ligands):

  1. Modification and sorting in the Golgi.
  2. Formation of secretory vesicles that bud from the trans‑Golgi network.
  3. Microtubule‑based transport (kinesin motors) to the plasma membrane.

• Exocytosis: Vesicle docks at the plasma membrane, SNARE proteins mediate membrane fusion, and the ligand is released into the ECF or bloodstream.

2. Transport of Ligands to Target Cells

• Pathways:

  • Diffusion through the ECF – short‑range (autocrine, paracrine) signals.
  • Circulatory transport in blood plasma – endocrine hormones.

• Transport mechanisms:

  • Simple diffusion – small, lipophilic molecules (e.g., steroid hormones).
  • Carrier / binding proteins – hydrophobic hormones bound to albumin or specific carriers (e.g., thyroxine‑binding globulin).
  • Protection in vesicles or association with transport proteins for larger peptide hormones.

• Termination of the signal in the medium:

  • Enzymatic degradation (e.g., acetylcholinesterase hydrolyses acetylcholine).
  • Uptake and clearance by target or neighbouring cells.

3. Binding of Ligands to Cell‑Surface Receptors on Target Cells

• Receptor families required by the Cambridge syllabus (with human examples):

  • G‑protein‑coupled receptors (GPCRs) – 7‑transmembrane α‑helices; extracellular ligand‑binding site, intracellular loops interact with heterotrimeric G‑proteins.
    Example: β‑adrenergic receptor (binds adrenaline).
  • Receptor tyrosine kinases (RTKs) – single‑pass transmembrane proteins; extracellular ligand‑binding domain, intracellular tyrosine kinase domain that autophosphorylates.
    Example: Insulin receptor.
  • Ion‑channel‑linked receptors – ligand‑gated ion channels; ligand binding induces a conformational change that opens a pore for specific ions.
    Example: Nicotinic acetylcholine receptor.

• Ligand‑receptor interaction:

  • Specific binding (lock‑and‑key or induced‑fit) → conformational change in the receptor.
  • Activation of the intracellular domain:

    • GPCR → G‑protein activation.
    • RTK → autophosphorylation of tyrosine residues.
    • Ion‑channel → opening of the ion pore.

• Immediate cellular effects:

  • Opening/closing of ion channels → rapid changes in membrane potential.
  • Activation of enzyme cascades (e.g., phospholipase C, adenylate cyclase).

• Receptor regulation:

  • Endocytosis (receptor internalisation) – reduces signal strength.
  • Desensitisation – phosphorylation of GPCRs reduces G‑protein coupling.

Downstream Signal‑Transduction Cascade (Second Messengers)

• Key second messengers:

  • cAMP – produced by adenylate cyclase (GPCR‑Gs); activates protein kinase A (PKA).
  • IP₃ & DAG – produced by phospholipase C (GPCR‑Gq); IP₃ releases Ca²⁺ from the endoplasmic reticulum, DAG activates protein kinase C (PKC).
  • Ca²⁺ ions – act as a second messenger in many pathways (muscle contraction, neurotransmitter release).

• Amplification: One activated receptor can generate many second‑messenger molecules; each second messenger can activate multiple downstream enzymes, producing a large response from a small initial signal.
• Feedback control:

  • Negative feedback – phosphodiesterases degrade cAMP; protein phosphatases de‑phosphorylate kinases.
  • Positive feedback – Ca²⁺‑induced Ca²⁺ release amplifies the calcium signal.

• Cellular outcomes (examples):

  • Gene expression – activation of transcription factors (e.g., MAP‑kinase cascade → c‑Fos).
  • Metabolic regulation – activation/inhibition of key enzymes (e.g., glycogen phosphorylase).
  • Altered ion flux – changes in membrane potential, muscle contraction, secretion.

• Signal termination:

  • Degradation of second messengers (cAMP → AMP, IP₃ → IP₂).
  • Re‑phosphorylation or de‑phosphorylation of receptors.
  • Removal of ligand by enzymes or re‑uptake transporters.

Integrated Sequence of Events

1. Synthesis of ligand in the signalling cell (ribosome → ER → Golgi).
2. Packaging into secretory vesicles and transport to the plasma membrane.
3. Exocytosis – ligand released into the extracellular fluid or bloodstream.
4. Transport of ligand to the target cell (diffusion, carrier proteins, circulation).
5. Specific binding of ligand to a cell‑surface receptor (GPCR, RTK or ion‑channel‑linked).
6. Receptor activation → generation of second messengers → signal amplification.
7. Cellular response (gene expression, enzyme activation, ion‑channel opening, etc.).
8. Termination of the signal by ligand degradation, receptor desensitisation, phosphatases or second‑messenger breakdown.

Quick‑Check Question (AO2)

Which stage of cell signalling would be most affected by a mutation that blocks the function of SNARE proteins, and why?

Answer: Stage 1 – synthesis and secretion. SNARE proteins are essential for the docking and fusion of secretory vesicles with the plasma membrane during exocytosis; a block would prevent ligand release.

Summary Table of the Three Main Stages

Suggested Diagram (for revision)

A flow‑chart showing (1) ligand synthesis in the donor cell, (2) vesicular release into the extracellular space, (3) transport through blood or interstitial fluid, (4) binding to a membrane receptor on the target cell, and (5) downstream second‑messenger cascade within the target cell, all illustrated against a fluid‑mosaic membrane background.